Stimulus or heat applied to the skin can cause pain. The transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is a receptor that plays an important role in transmission and modulation of pain. It is mainly found in the nociceptive neurons of the peripheral nervous system (PNS), particularly in the sensory C-fiber and A-fiber neurons. It is also expressed in inflammatory cells, keratinocytes, etc. Well-known activators of TRPV1 include heat higher than 43° C., capsaicin, the pungent compound in hot pepper, acidic condition (low pH), endocannabinoid, anandamide and N-arachidonoyl-dopamine. When activated by these stimulants, TRPV1 acts as an ion channel that allows influx of Ca2+ into cells. The Ca2+ influx leads to signal transductions causing pain and burning sensation. In addition, it is known that TRPV1 is activated by mitogen-activated protein kinase (MAPK) signaling pathways by nerve growth factor (NGF), bradykinin, prostaglandin 2 (PGE2), tumor necrosis factor-α (TNF-α), etc. leading to Ca2+ influx into cells.
When the skin temperature is about 42° C., recovery of the skin barrier proceeds slowly. In this case, treatment with the TRPV1 antagonist capsazepine restores the rate of skin barrier recovery to normal level. The heat produced during the laser treatment recently performed by dermatology clinics increases the skin temperature to about 45-50° C. This causes pain, which is thought to be transmitted by the TRPV1 receptor. However, not all the TRPV1 antagonists are effective to relieve the pain caused by the laser treatment.
Accordingly, there is a need of development of a substance among the TRPV1 antagonist that effectively relieves skin irritation or pain and facilitates skin barrier recovery after the laser treatment.